To study the separate and combined effects of the sensorimotor aspects of cigarette smoking and the pharmacologic effects of nicotine, 80 smokers rated the subjective effects of nicotine infusion (continuous infusion or pulsed injections) vs saline infusion, and de-nicotinized cigarettes vs no-smoking, in a 3 X 2 design. A seventh condition presented high nicotine cigarette smoke (usual brand). The dose and rate of nicotine administration in all conditions were equated to those of ad lib smoking after overnight abstinence, as measured in a previous baseline session. De-nicotinized cigarette smoke significantly reduced craving and was rated as significantly more satisfying and rewarding than nicotine infusions. Intravenous nicotine also reduced craving for cigarettes, as well as increasing ratings of lightheadedness and dizziness. There was no significant euphoria associated with nicotine infusions. The combination of intravenous nicotine and smoking a de-nicotinized cigarette produced effects similar to those of smoking a high-nicotine cigarette. These results suggest that sensorimotor factors are critical in producing the immediate subjective response to smoking and that the immediate positive subjective consequences of nicotine, in doses similar to those obtained from cigarette smoke, are subtle.